Parkinson's Disease Essay

AD is a progressive age-related neurodegenerative disorder that poses increasing challenges to the global healthcare system and economic development. AD is characterized by extracellular neurotic plaques composed of Aβ deposits and intracellular neurofibrillary tangles composed of hyperphosphorylated tau with progressive loss of synapses in the brain [1]. Evidence demonstrates a potential link between oxidative stress, mitochondrial dysfunction and AD development [2]. Oxidative damage has been known to occur at a very early stage of AD even prior to Aβ plaque formation and the onset of symptoms [3, 4, 5]. Several cellular changes by oxidative stresses have been related with Aβ plaques formation and pathophysiological events of AD [6].

Ketone bodies appear to have a conceivable neuroprotective role in NDD by decreasing oxidative stress through reducing ATP production via indirect inhibition, changing mitochondrial energy metabolism by altering cellular communication, increasing antioxidant activity and reducing neuronal death (Gano, Patel, Rho 2014). Interest in investigating the probable connection between ketone bodies produced via KD and oxidative stress and mitochondrial dysfunction is on the rise. Next, a review of three current original studies exploring ketone bodies effect on the progression of several of the most notable NDD’s: AD, PD, and ALS, respectively.

In Parkinson's Disease and Huntington's disease the nigra-striatum neural communication assemblage is severely hampered. PD results from a depletion in the amount of dopamine produced by the brain. At the onset of the disease, dopamine-secreting cells of the substania nigra, either because of genetic factors or environmental toxins, experience mass cell death. Thus, the nigra cells are unable to form synapses through which they secrete and relay dopamine to the striatum in a neural circuit within the basal ganglia (18).

PD is the second most common neurodegenerative disease featured pathologically by the progressive loss of dopaminergic neurons in the substantia nigra. The typical symptoms of PD include slowness of movements (bradykinesia), muscle stiffness (rigidity), tremor, and balance disturbance. Etiopathologically, PD is considered to be caused by the significant loss of dopaminergic neurons in the substantia nigra pars compacta and the subsequent dopamine depletion at the striatum. To date, there are only symptomatic treatments available for PD, particularly in the early stages of the disease. No therapy has been found that can cure or halt the progression of the disease.

Oxidative stress and inflammation play a causative role in epileptogenesis and ictogenesis by taking part in neurodegeneration and excite-toxic neuronal injury (4-6). On the other hand, prolonged seizures lead to neuronal cell death by inducing mitochondrial dysfunction and incre-asing reactive oxygen species (ROS) and nitric oxide (NO). Moreover, ROS may prolong gluta-mate presence at synapses and result in further neurotoxicity (7).

Parkinson disease (PD) is one of the most common neurologic disorders. and it affects approximately 1% of individuals older than 60 years old. Parkinson’s disease is a condition that progresses slowly by treatment. In addition, loss of pigmented dopaminergic neurons of the substantianigra pars compacta and the presence of Lewy bodies and Lewyneurites are the two major neuropathologic findings in Parkinson disease (Hauser, 2016).

The major component shared by both Parkinson’s disease and dementia is the functioning of neurons, with a then understandable association. Dementia is caused by neuron demise or diminished capacity of communication with other cells, while Parkinson’s disease, neurons in the basal ganglia experience deterioration that disrupts the normal neurotransmitter dopamine balance where neurons waste and die. With this shared neuron deterioration, the prevalence of dementia associated with Parkinson’s disease is clearly understood. One-third of all patients with Parkinson’s disease will display dementia (LeMone, Burke, & Bauldoff, 2011) with indicators identical to Alzheimer’s form of dementia.

Attempts to cure or slow down the progression of Parkinson’s disease have largely failed; researchers in this paper maintain this is obviously a direct result of the lack of insight into the pathogenesis of the disease. Parkinson’s disease is the product of the deaths of a number of dopaminergic (dopamine-secreting) neurons in the substantia nigra pars compacta region (SNc) of the brain. But what causes these deaths? In the paper “‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease,” Chen and researchers find that older neurons in the SNc are unusually reliant on calcium channels and that after blocking these channels, the cells are “rejuvenated” and begin acting like their juvenile counterparts; as a

In spite of significant improvements in our knowledge of the pathogenesis of AD over recent decades, the precise mechanisms leading to AD development remain elusive. Over the years, several different hypotheses have been postulated to address the pathological lesions observed in AD. Indeed, oxidative stress has been consistently observed as an underlying biochemical anomaly in several neurodegenerative diseases including AD. However, whether oxidative stress presents a causal role or is secondary to AD pathogenesis remains unclear.[39] Markers for oxidative stress have been reported during early development of the disease and in patients with mild cognitive impairment well before the onset

Parkinson disease (PD), also referred to as Parkinson’s disease and paralysis agitans, is a progressive neurodegenerative disease that is the third most common neurologic disorder of older adults. It is a debilitating disease affecting motor ability and is characterized by four cardinal symptoms: tremor rigidity, bradykinesia or kinesis (slow movement/no movement), and postural instability. Most people have primary, or idiopathic, disease. A few patients have secondary parkinsonian symptoms from conditions such as brain tumors and certain anti-psychotic drugs.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized mainly by physical and psychological disabilities. This disorder was named after James Parkinson, an English physician who first described it as shaking palsy in 1817 (Goetz, Factr, and Weiner, 2002). Jean- Martin Charcot, who was a French neurologist, then progressed and further refined the description of the disease and identified other clinical features of PD (Goetz, Factr, and Weiner, 2002). PD involves the loss of cells that produce the neurotransmitter dopamine in a part of the brain stem called the substansia nigra, which results in several signs and symptoms (Byrd, Marks, and Starr, 2000). It is manifested clinically by tremor,

Parkinson’s Disease is known as one of the most common progressive and chronic neurodegenerative disorders. It belongs to a group of conditions known as movement disorders. Parkinson disease is a component of hypokinetic disorder because it causes a decreased in bodily movement. It affects people who are usually over the age of 50. It can impair an individual motor as well as non-motor function. Some of the primary symptoms of Parkinson’s disease are characterized by tremors or trembling in hands, legs and arms. In early symptoms the tremor can be unilateral, appearing in one side of body but progression in the disease can cause it to spread to both sides; rigidity or a resistant to movement affects most people with Parkinson’s disease,

Diagnosis of Parkinson’s Disease is extremely important in terms of treating the symptoms before the disease gets worse. It is common for patients with PD to have motor symptoms such as gait disorder, which comes from muscle stiffness/rigidity, bradykinesia, postural imbalance, etc. Gait disorders can generally help determine how far the neurological disorder has affected the motor function and control of the individual. Many physicians in general clinics determine if a patient has PD or if it has progressed through evaluating the patients gait pattern, focused on a direct path walking. The problem with this way of diagnosis is that direct paths would generally require the clinic to have a space of 100-meter length for the patient to walk;

Parkinson’s disease is affected by the degeneration of dopaminergic neurons which is responsible to produce dopamine. Dopaminergic neurons have their cell bodies in substantia nigra pars compacta (SNpc) in basal ganglia (O’Sullivan and Schmitz, 2007). Basal ganglia are a collection of interconnected gray matter nuclear masses deep within the brain”. These gray matter masses are caudate, putamen, globus pallidus, subthalamic nucleus and the substantia nigra. Basal ganglia receive its input through striatum (O’Sullivan and Schmitz, 2007).

C.1. Mouse PD model to be used in this project: In VMAT2 LO, a transgenic mouse PD model, shut-down of 95% endogenous vesicular monoamine transporter 2 (VMAT2) leads to a massive oxidative deamination of monoamine neurotransmitters [43], accompanied by increased oxidative stress markers and a significant decrease of antioxidant ability [44]. Therefore, oxidative damage could be the culprit for the replication of the pathogenic features of PD [45], including substantial reductions of DA and NE levels in the brain, progressive neurodegeneration in the SNpc and LC with formation of α–synuclein containing inclusions. More importantly, neuronal loss in the LC of VMAT2 LO mice starts earlier (at 12 months) and to a greater extent